Human Mesenchymal Stem Cells For Infants At High Risk For Bronchopulmonary Dysplasia

• ClinicalTrials.gov Identifier: NCT03774537
• Recruitment Status: Unknown
• First Posted: December 13, 2018
• Last Update Posted: March 6, 2019
• Sponsor: Children's Hospital of Chongqing Medical University
• Information provided by (Responsible Party): Xia Yunqiu, Children's Hospital of Chongqing Medical University

Tracking Information

• First Submitted Date: December 12, 2018
• First Posted Date: December 13, 2018
• Last Update Posted Date: March 6, 2019
• Actual Study Start Date: March 1, 2019
• Estimated Primary Completion Date: December 1, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 12, 2018)

Number of participants with adverse reactions related to infusion after treatment [ Time Frame: 24 hours after administration ]

To evaluate the safety of hUC-MSCs for BPD.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 12, 2018)

• The incidence and severity of BPD defined by the National Institutes of Child Health and Human Development (NICHD) workshop. [ Time Frame: at the corrected gestational age of 36 weeks ]
  To evaluate the efficacy of hUC-MSCs to prevent preterm infants at high risk of BPD from developing BPD
• Changes of high-resolution chest CT in participants [ Time Frame: within 2 years after administration ]
  To evaluate the safety and efficacy of human umbilical cord -derived mesenchymal stem cells for BPDmesenchymal stem cells for BPD.
• Changes of temperature in participants [ Time Frame: 3 days after administration ]
  To evaluate the safety of human umbilical cord -derived mesenchymal stem cells for BPD.mesenchymal stem cells for BPD.
• Changes of blood pressure in participants [ Time Frame: 3 days after administration ]
  To evaluate the safety of human umbilical cord -derived mesenchymal stem cells for BPD. Blood pressure is measured by electronic sphygmomanometer.
• Changes of respiratory rate in participants [ Time Frame: 3 days after administration ]
  To evaluate the safety of human umbilical cord -derived mesenchymal stem cells for BPD.
• Changes of oxygen saturation in participants [ Time Frame: 3 days after administration ]
  To evaluate the safety of human umbilical cord -derived mesenchymal stem cells for BPD.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Human Mesenchymal Stem Cells For Infants At High Risk For Bronchopulmonary Dysplasia
• Official Title: Intravenous Human Umbilical-Cord-Derived Mesenchymal Stem Cells For Premature Infants Ａt High Risk For Bronchopulmonary
• Brief Summary: This study is an open-label, single-center, dose escalation study to evaluate of safety and efficacy of human umbilical cord -derived mesenchymal stem cells (hUC-MSCs) in premature infants at high risk for Bronchopulmonary Dysplasia（BPD）

Detailed Description

BPD is a chronic lung disease that occur in premature infants receiving prolonged oxygen pulmonary and ventilator therapy. It remains a main complication of extreme prematurity and currently lacks efficient treatment.The mortality rate of one year after birth is still high and the quality of life is not optimistic.

hUC-MSCs are widely used in clinic due to their low immunogenicity and convenient to get. Many animal study had shown that hUC-MSCs had therapeutic effects on a variety of animal models of lung disease.Furthermore,there are a large number of clinical trials of MSCs applied to various system diseases and the safety was verified.So, the main purpose of this study is to evaluate the safety and efficacy of hUC-MSCs in participants at high risk for BPD

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Bronchopulmonary Dysplasia

Intervention

• Drug: Transplantation of hUC-MSCs
  Preterm infants at high risk for BPD will receive transplantation of hUC-MSCs through intravenous infusion. Dose A - 1 million cells per kg; Dose B - 5 million cells per kg
  Other Name: Intravenous infusion of hUC-MSCs
• Drug: No transplantation of hUC-MSCs
  Preterm infants at high risk for BPD will not receive transplantation of hUC-MSCs
  Other Name: No intravenous infusion of hUC-MSCs

Study Arms

• Experimental: Transplantation of hUC-MSCs
  Preterm infants at high risk for BPD will receive transplantation of hUC-MSCs.
  Intervention: Drug: Transplantation of hUC-MSCs
• No transplantation of hUC-MSCs
  Preterm infants at high risk for BPD will not receive transplantation of hUC-MSCs
  Intervention: Drug: No transplantation of hUC-MSCs

Publications *

• Chang YS, Ahn SY, Yoo HS, Sung SI, Choi SJ, Oh WI, Park WS. Mesenchymal stem cells for bronchopulmonary dysplasia: phase 1 dose-escalation clinical trial. J Pediatr. 2014 May;164(5):966-972.e6. doi: 10.1016/j.jpeds.2013.12.011. Epub 2014 Feb 6.
• Hayes D Jr, Meadows JT Jr, Murphy BS, Feola DJ, Shook LA, Ballard HO. Pulmonary function outcomes in bronchopulmonary dysplasia through childhood and into adulthood: implications for primary care. Prim Care Respir J. 2011 Jun;20(2):128-33. doi: 10.4104/pcrj.2011.00002. Review.
• Ahn SY, Chang YS, Kim JH, Sung SI, Park WS. Two-Year Follow-Up Outcomes of Premature Infants Enrolled in the Phase I Trial of Mesenchymal Stem Cells Transplantation for Bronchopulmonary Dysplasia. J Pediatr. 2017 Jun;185:49-54.e2. doi: 10.1016/j.jpeds.2017.02.061. Epub 2017 Mar 21.
• Wilson JG, Liu KD, Zhuo H, Caballero L, McMillan M, Fang X, Cosgrove K, Vojnik R, Calfee CS, Lee JW, Rogers AJ, Levitt J, Wiener-Kronish J, Bajwa EK, Leavitt A, McKenna D, Thompson BT, Matthay MA. Mesenchymal stem (stromal) cells for treatment of ARDS: a phase 1 clinical trial. Lancet Respir Med. 2015 Jan;3(1):24-32. doi: 10.1016/S2213-2600(14)70291-7. Epub 2014 Dec 17.
• Laube M, Stolzing A, Thome UH, Fabian C. Therapeutic potential of mesenchymal stem cells for pulmonary complications associated with preterm birth. Int J Biochem Cell Biol. 2016 May;74:18-32. doi: 10.1016/j.biocel.2016.02.023. Epub 2016 Feb 27. Review.
• Pierro M, Ionescu L, Montemurro T, Vadivel A, Weissmann G, Oudit G, Emery D, Bodiga S, Eaton F, Péault B, Mosca F, Lazzari L, Thébaud B. Short-term, long-term and paracrine effect of human umbilical cord-derived stem cells in lung injury prevention and repair in experimental bronchopulmonary dysplasia. Thorax. 2013 May;68(5):475-84. doi: 10.1136/thoraxjnl-2012-202323. Epub 2012 Dec 4.
• Hansmann G, Fernandez-Gonzalez A, Aslam M, Vitali SH, Martin T, Mitsialis SA, Kourembanas S. Mesenchymal stem cell-mediated reversal of bronchopulmonary dysplasia and associated pulmonary hypertension. Pulm Circ. 2012 Apr-Jun;2(2):170-81. doi: 10.4103/2045-8932.97603.
• Yeh TF, Chen CM, Wu SY, Husan Z, Li TC, Hsieh WS, Tsai CH, Lin HC. Intratracheal Administration of Budesonide/Surfactant to Prevent Bronchopulmonary Dysplasia. Am J Respir Crit Care Med. 2016 Jan 1;193(1):86-95. doi: 10.1164/rccm.201505-0861OC.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: December 12, 2018): 20
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2021
• Estimated Primary Completion Date: December 1, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. An infant whose postnatal age is 3 to 14 days, inclusive (for treatment between 5 and 14 days after birth)
2. Gestational age is between 23 and 28 weeks (23 weeks ≤ gestational age (GA) < 28 weeks)
3. Birth weight is between 500g and 1000g, inclusive
4. Being intubated and receiving mechanical ventilation within 5-14 days after birth, with a fraction of inspired oxygen (FiO2) of 0.25 or greater at Screening
5. Written consent form signed by a legal representative or a parent.

Exclusion Criteria:

1. Although mechanical ventilation or oxygen is required in participants, there are no signs of dyspnea or BPD-related changes in lung imaging, such as central apnea or diaphragm paralysis.
2. The participants who have complex congenital heart disease.
3. The participants who have severe pulmonary hypertension(cardiac ultrasound confirmed) at the time of assessment.
4. The participants who have severe respiratory tract malformation: pierre-robin syndrome, tracheobronchomalacia, vascular ring syndrome, congenital tracheal stenosis, tracheo-esophageal fistula, pulmonary emphysema, pulmonary sequestration, congenital pulmonary dysplasia, congenital pulmonary cyst, congenital spasm, etc.
5. The participants who have severe chromosome anomalies :Edward syndrome, Patau syndrome, Down syndrome, etc) or severe congenital malformation (Hydrocephalus, Encephalocele, etc).
6. The participants who have severe congenital infection(Herpes, Toxoplasmosis, Rubella, Syphilis, AIDS, etc).
7. The participants who have severe sepsis or shock.
8. The participants who is going to have surgery 72 hours before/after this study drug administration.
9. The participants who have surfactant administration within 24 hours before this study drug administration.
10. The participants who have severe intracranial hemorrhage ≥ grade 3 or 4.
11. The participants who have active pulmonary hemorrhage or active air leak syndrome at the time of assessment.
12. The participants who have the history of other clinical studies as a participant.
13. The participants who is considered inappropriate by the investigators.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: up to 14 Days (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT03774537
• Other Study ID Numbers: XiaYQ
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Xia Yunqiu, Children's Hospital of Chongqing Medical University
• Study Sponsor: Children's Hospital of Chongqing Medical University
• Collaborators: Not Provided

Investigators

• Study Chair: Zhou Fu; Children's Hospital of Chongqing Medical University

• PRS Account: Children's Hospital of Chongqing Medical University
• Verification Date: March 2019